Substance abuse, psychiatric disorders, HIV/AIDS, and homelessness are pressing public health concerns. Homeless young adults are at especially high risk for substance abuse, psychiatric disorders, and HIV infection. Understanding the relationships of these problems in this vulnerable population, and using this knowledge to inform the development of interventions to reduce substance abuse and HIV risk behaviors is crucial. My overarching aim for this Mentored Patient-Oriented Research Career Development Award (K23) award is to gain expertise developing and testing disseminable brief interventions to reduce substance and HIV risk behaviors in homeless young adults, an underserved and under-researched population. To succeed, I will require protected time. My training objectives are to develop a greater knowledge base in research on substance abuse, psychiatric disorders, and HIV risk behaviors. Specifically, I propose training on (a) study design, including randomized clinical trials, and sample selection; (b) biostatistics, specifically longitudinal data analysis; (c) assessment of psychiatric comorbidity, substance abuse outcomes, and their relationship; and (d) evidence-based interventions for substance abuse and substance reduction. The proposed research plan, combining clinical and public health research, will provide an opportunity to apply my training and lead to the development of brief interventions to reduce substance abuse and HIV risk behaviors in homeless young adults. Study 1 has two main components. The first, Study 1A, involves analyses of data from a pilot randomized trial to test the One Plus One (OPO), a 2-session, individual motivation-based intervention I designed to reduce drinking and HIV risk among homeless adolescents who exited foster care. The analyses will allow me to evaluate whether OPO affects substances other than alcohol, and whether participant baseline psychiatric status influences OPO dropout, substance, and HIV outcomes. Using these findings, I will design and conduct Study 1B, in which I will modify OPO to target illicit substances in addition to alcohol, adapt the design as necessary, and conduct a second small randomized trial to test feasibility and preliminary effectiveness of the revised OPO. This second small trial will provide the basis for an application for an R01- funded larger trial to test the efficacy of the revised OPO. To place my clinical research within a larger public health framework and to inform the development of OPO, I will also conduct Study 2. This will involve investigation of the relationships between substance and psychiatric disorders, HIV risk, and homelessness in a large national sample with a 3-year follow-up. Using these data, I will analyze factors affecting the risk of drinking alcohol before sexual activity (Study 2A) and the roles of socioeconomic status, substance abuse, and psychiatric disorders on the prospective likelihood of becoming homeless (Study 2B). This research plan will allow me to realize the potential of my clinical experience and research ideas to help reduce substance abuse and HIV risk behaviors among the population of homeless young adults who are badly in need of assistance.